Mouse Models of Metastasis and Dormancy

Abstract

Metastasis is the ultimate and often lethal stage of cancer. Metastasis occurs in three phases that may vary across individuals: First, dissemination from the primary tumor. Second, tumor dormancy at the metastatic site where micrometastatic cancer cells remain quiescent or, in dynamic cycles of proliferation and elimination, remaining clinically undetectable. Finally, cancer cells are able to overcome microenvironmental constraints for outgrowth, or the formation of clinically detectable macrometastases that colonize distant organs and are largely incurable. A variety of approaches have been used to model metastasis to elucidate molecular mechanisms and identify putative therapeutic targets. In particular, metastatic dormancy has been challenging to model in vivo due to the sparse numbers of cancer cells in micrometastasis nodules and the long latency times required for tumor outgrowth. Here, we review state-of-the art genetically engineered mouse, syngeneic, and patient-derived xenograft approaches for modeling metastasis and dormancy. We describe the advantages and limitations of various metastasis models, novel findings enabled by such approaches, and highlight opportunities for future improvement.